Tuesday, December 25, 2012

The Elfin genome project (EGP)

We annually hear about Santa Claus and his world travels.  It may be thrilling or enthralling to kids, but why he goes in an open sleigh with some dowdy reindeer pulling him around in the age of Business Class travel is a mystery for us adults to ponder.  With his agenda, Santa would quickly earn enough frequent flyer points to qualify for early Red Carpet boarding and more leg (and belly) room than we ordinary folks can more than dream of.  Instead, Mr Claus stubbornly sticks to his antediluvian transport.  Why is that, we wonder?

An obvious answer is that he would have to check in so much baggage that the usual panoply of  plastic fall-apart toys would cost more to check, at $25 each, than they were worth in the first place.  Reindeer would seem a rather malodorous and awkward kind of 'engine' to maintain, especially for 364 days a year, getting only one night's use from them.  Aircraft have to be used more often than that, to keep their parts oiled, but at least they get around faster and with more comfort.  In the latter regard, as an old man like Santa should note, that also means more 'comfort' facilities (i.e., rest rooms).  Think what it must be to be Santa, and in house after house after house: each one provides a drink and cookies, but he must start having bladder retention issues after the first few hundred homes.

We could go on, but you probably get the point.  Instead, there is a serious scientific issue that the Good St N raises.  For centuries we've been told that these little toys and other gifts are manufactured in the polar cold by a bunch of 'elves'.

Norman Rockwell, Sat Evening Post, 1922; Wikimedia

The Elfin genome Project (EGP)
 Elves are portrayed as very miniature, pointy-eared people.  They have shoes with pointy toes and wear clothes that seem to be in a rather Alpine style.  Yet they are never seen by we who are the recipients of their good work.  They are normal-looking rather than microcephalic or of any anomalous stunted growth.  They are smaller than the African Ituri ('pygmies') or San ('bushmen'), Mexican Mayans or Amazonian Yanomami, but they appear roughly 'European' in physiognomy.  They are often portrayed as congenially middle-aged, and as far as we know are all males.  We are not told if they have children, or parents, or if there is anyone around to serve as feminine company.  Many questions are thus raised.

Surely it would be important to find out what their genomes may reveal about their traits and their ancestry!  It would be, one might dare suggest, vastly more important than the results of the latest GWAS or whole genome sequencing study of ordinary humans, when we know just what kind of 'revolutionary' data (as the major journals like the NY Times daily report) such studies provide us.

An Elfin Genome Project (EGP) would, by contrast, be truly transformative of our understanding of 'human' (if they are human) evolution and variation.  Clearly elfin stature and traits are not just normal but quite positively to their benefit, so the selective history that is responsible--and where that adaptive evolution to diminutiveness occurred--would be of major value to human geneticists who are currently flailing around trying to make major careers out of incremental enumeration of polygenes for traits that aren't really genetic in the first place.
(image from http://www.minibite.com/christmas/allyouneediselves.htm)

These days, it would not cost very much for the EGP to do an entire elfin genome sequence, which could be done in any self-respecting human genetics lab sporting 'Next-Generation' sequencing equipment.  The EGP would provide not just the raw genome sequence of 'the elf', but would be immediately aligned to 'the' human genome sequence and those of other primates, to see just where these little guys fit, in the branching tree of descent.  Would they appear to be recently diverged from, say, Scandinavians?  Swiss?  Or more distantly related to the very short-statured Pacific Homo floresiensis (the 'Hobbits') fossils found on a southeast Asian island?

Translational medicine for the elfin population
We would of course entrust to NIH-funded researchers the job of identifying disease genes that would quickly be discovered in the EGP sequence.  Whether or how one could get treatment delivered to any such person is not so clear.  However, NIH is absolutely determined to have another named Project they can promote to justify their funding, and the EGP data could fit right into their Translational Medicine 'offensive'--no pun intended, though it implies that previous NIH work was never actually  about helping with health and disease.  The claim is that NIH will actually now (finally!) try to 'translate' research findings into clinical practice and benefit.  But since human genetics has in fact always been largely about  improved medical care since Archibald Garrod founded the profession around 1900--by studying alkaptonuria and other metabolic genetic diseases--NIH"s highly publicized "translation" project might be viewed (by a cynic) as yet another image-enhancing hype designed to persuade Congress to increase their budget, rather than much that is actually new.  We would never subscribe to such cynicism, however.

On the other hand we can suggest a legitimate Translation project, for the elves, based on the EGP.  For example, we could leave pills or an appropriately filled syringe, along with the cookies and milk, for Santa to take back and administer to the affected elf.  However, this would assume that 'the' elf genome we would get from one sample represents all of them.  That would be tantamount to saying that, for example, being very short and jolly was a genetic disorder requiring 'treatment'.  Of course, these days people seem determined to characterize just about everything as genetic, so that wouldn't be so surprising.  Or, such universal treatment would suggest that if you've seen one elf you've seen 'em all.  No, no; much better to have many sequences from different elves, to find out which of them suffered from, or we could predict will suffer from, any number of terrifying diseases, other than runtiness, for some of which we might have translational treatment such as suggested above, but for others at least we could warn them that they were a ticking time bomb, and just hope they wouldn't worry about it too much and start sabotaging the toys they make.

There is a problem here, of course.  Since we don't actually know where Santa and the elves live, we would not know where to send a hit-and-run medical team to collect blood and get signed informed consent from the elves, that (as is the current practice) ceded to the investigators any profits from developing the 'translation' research the subjects' taxes are paying for--or even what language to write such a legalistic document in.

Santa's not there!
Unfortunately, rumors that Santa & Co. live at the North Pole are greatly exaggerated. Recent expeditions to the pole have discovered, exposed by the melting snow due to climate change, huge piles of unopened letters to Santa from children, requesting toys that never actually showed up under the tree (how the parents rationalize this to their disappointed children is a separate question).  Santa could not be so cruel as to give a North Pole mail drop but never to visit the site, without a good reason. Maybe he figured most of the mail would be--as it is for the rest of us--tasteless and often misleading advertising solicitations and bills, and he just would rather be able to say "Gee, I never saw that bill for sleigh repair or reindeer-feed and jingle bells".

But wherever he and his impish crew actually live, science knows how to be intrusive and can outsmart him, yes, even Santa.  In his genial approach, he accepts the bag of gifts wrapped by the elves rather than he or the Missus doing the packing themselves.  Now we know that when the elves made or wrapped these products, all sorts of their DNA would have settled onto the materials (e.g., in flakes of dandruff from their bearded chins).  Any forensic team worthy of a CSI designation could easily wipe these toys, paper, and ribbons and obtain spitloads of DNA, for analysis in their labs.

So, the EGP is possible!  Any of you whose lab personnel have little to do this holiday season (meaning that your Dec 1 grant application's in and the Jan 1 ones are more or less written), and may be idle enough to be reading this post, should hasten to start the EGP, and get the jump on your competition--then you'll get a huge grant as your Christmas present (and from Francis Collins, not some puny elf or pudgy, aging, silly sleigh-riding multi-centenarian).  So, get started!

A sad, parting thought, however
Finally, on another note, we must wonder whether the ice caps and snow-melt will cause problems for Santa's deer, elves, sleigh, or even his home?  Could his good Ms Claus be pestering him to relocate to a more salubrious clime?  Could a retirement home be in her thinking?  With Obamacare in the offing, they would not have to worry about their medical welfare, even though they, not being elves, wouldn't benefit from the EGP.

We'll leave you to ponder that, over what we hope will be a Merry Christmas and a delicious dinner with friends or family!

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